Existing topical treatments for actinic keratosis (AK) have different dosage regimens. Many treatment regimens extend over weeks or months.
The compound ingenol-3-angelate (also known as ingenol mebutate, PEP005, or (1aR,2S,5R,5aS,6S,8aS,9R,10aR)-5,5a-dihydroxy-4-(hydroxymethyl)-1,1,7,9-tetramethyl-11-oxo-1a,2,5,5a,6,9,10,10a-octahydro-1H-2,8a-methanocyclopenta[a]cyclpropa[e][10]annulen-6-yl(2Z)-2-methylbut-2-enoate; Sayed, M. D. et. al.; Experienta, (1980), 36, 1206-1207)) can be isolated from various Euphorbia species. Specifically, ingenol mebutate can be isolated from Euphorbia peplus (Hohmann, J. et al., Planta Med., (2000), 66, 291-2940)) and Euphorbia drummondii by extraction followed by chromatography, e.g., as described in U.S. Pat. No. 7,449,492.
Picato® (ingenol mebutate topical gel), which is approved in many countries around the world for treatment of actinic keratosis, is available at two dosage strengths (0.015% and 0.05%) and is administered for two or three consecutive days, depending on the location of the actinic keratosis lesions; the concentration of the active compound differs depending on the location of the actinic keratosis lesions. For lesions located on the head (for example, the face or scalp), the approved dose is 0.015% ingenol mebutate applied for 3 consecutive days. For lesions located on a ‘non-head’ region (for example, the forearm or back), the approved dose is 0.05% ingenol mebutate applied for 2 consecutive days (see also Lebwohl et al., 2012, New England Journal of Medicine, 366: 1010-9).
The approved indications for PICATO provide that the topical gel can be applied to a contiguous area of up to 25 cm2. Although pharmacokinetic studies were conducted on areas of the forearm as large as 100 cm2, efficacy on areas greater than 25 cm2 was not measured. However, often the AK lesions are found in larger areas of skin, so there is a need for a product to treat larger areas.